Optical flow cell and test head apparatus

ABSTRACT

A sample cell apparatus for use in spectroscopic determination of an analyte in a body fluid sample includes a first plate member made from an optically clear material and a second plate member made from an optically clear material and opposing the first plate member. A channel extending into a surface of the first plate member and an opposing surface of the second plate member houses a floating seal. The floating seal surrounds a fluid chamber that retains a sample of body fluid for optical measurement. The fluid chamber may be opened for flushing by separating the first plate member from the second plate member. During measurements the fluid chamber is closed to define a repeatable optical path-length therethrough by urging the first plate member against the second plate member without compressing the floating seal between the first plate member and the second plate member.

FIELD OF TECHNOLOGY

Aspects of the present disclosure are directed to the field ofspectroscopic determination of analyte content in a sample, and moreparticularly to the field of presenting a body fluid sample forspectroscopic analysis in an optical flow cell.

BACKGROUND

In a variety of clinical settings, it is important to measure certainchemical characteristics of blood, for example, the analytes Hemoglobin(e.g., Carboxyhemoglobin, Oxyhemoglobin, Methemoglobin), proteins,lipids, bilirubin. These settings range from a routine visit of apatient to a physician's office, an emergency room, or monitoring of ahospitalized patient, for example. Measurement of an analyte in a bodyfluid sample may be accomplished by numerous methods one of which is byspectroscopic determination.

Spectroscopic determination of analyte content in a body fluid sample,such as a blood sample for example, involves presenting the body fluidsample to a light source and analyzing properties of light transmittedthrough the sample or reflected from the sample. A structure forpresenting a fluid sample in a spectroscopic measurement instrument suchas a clinical analyzer is generally called an optical flow cell. Incertain implementations, a sample chamber in the sample cell ispreferably configured with a precise depth dimension during measurementsso that a path-length of light through the sample is predetermined. Theoptical path-length through an optical flowcell may preferably bemaintained within a few microns during a measurement, for example.Following a measurement, the sample may be flushed from the flow cell toprepare for analysis of another sample. During the flushing process theoptical flow cell may be opened or partially opened for more efficientflushing, for example.

Two alternative sample cell configurations for optical spectroscopy aspreviously known are described in U.S. Pat. No. 6,188,474. In oneconfiguration, a previously described sample cell is selectivelyadjustable between a first position having a predetermined opticalpath-length adapted for analyte measurement while the sample is in themeasurement zone, and a second position having a predetermined otherpath-length adapted for clearing the sample from the flow path. Thispreviously known sample cell includes two cell portions that aremaintained in a slidable fluid tight engagement with one another so thatadjustability of the fluid flow path from a small cross section flowpath for measurement to a larger cross section flow path for flushing isaccomplished by sliding the mating surfaces relative to another. Theslidable engagement in this configuration detrimentally may trap sampleportions between the first cell portion and the second cell portionwhich may cause contamination to a sample under measurement and mayaffect the dimensional consistency of the path-length. In anotherconfiguration, the previously described sample cell is selectivelyadjustable between a first position having a predetermined opticalpath-length for measurement and a second position for clearing thesample by applying and relaxing a compressive force between the firstcell portion and the second cell portion. In this configuration, thepath-length may be detrimentally affected by compression of anelastomeric gasket between the first cell portion and a second cellportion.

SUMMARY

Aspects of the present disclosure include a variable path length opticalflow cell such as the type of optical flow cell used for measuring ananalyte in a clinical analyzer. The analytes are typically found in abody fluid including but not limited to blood, plasma and serum.Analytes measured in optical flow cell include but are not limited toHemoglobins, proteins, lipids, and bilirubin, for example. The disclosedflow cell expands and closes like a bellows to achieve a first depth forcleaning and a shallower second depth for measurement. In oneembodiment, sealing in the disclosed flow cell is achieved by a diamondshaped seal surrounding an inner fluid chamber. The diamond shaped sealis operative to seal the inner fluid chamber by expanding laterallyagainst walls of a seal channel containing the seal in the flow cellthroughout the movement of the two portions of the optical flow cell.The seal is not compressed between the first portion of the cell and thesecond portion of the cell. This improves precision and repeatability ofan optical path-length through the flow cell.

BRIEF DESCRIPTION OF THE DRAWINGS

The foregoing will be apparent from the following more particulardescription of example embodiments of the present disclosure, asillustrated in the accompanying drawings in which like referencecharacters refer to the same parts throughout the different views. Thedrawings, which are not necessarily to scale, emphasis illustrativeembodiments of the present disclosure.

FIGS. 1A-1C illustrate an example of an optical flow cell according toan aspect of the present disclosure.

FIG. 2 illustrates an optical flow cell including cantilever armsconfigured to provide an opening force between portions of the opticalflow cell according to an aspect of the present disclosure.

FIG. 3 illustrates a test head apparatus for locating and actuating anoptical flow cell according to an aspect of the present disclosure.

FIG. 4 illustrates a test head apparatus for locating and actuating anoptical flow cell according to another aspect of the present disclosure.

FIG. 5 illustrates a test head apparatus for locating and actuating anoptical flow cell according to another aspect of the present disclosure.

FIG. 6 is a graph of test data illustrating optical path lengthrepeatability in a test head apparatus according to an aspect of thepresent disclosure.

FIG. 7 illustrates a test head apparatus for locating and actuating anoptical flow cell according to another aspect of the present disclosure.

FIG. 8 is a process flow diagram describing a method for spectroscopicdetermination of an analyte in a body fluid sample, according to anaspect of the present disclosure.

DETAILED DESCRIPTION

Aspects of the present disclosure include a variable path length opticalflow cell for optical measurement of analytes in a body fluid sample ina clinical analyzer such as but not limited to GEM 4000 and GEM 5000clinical analyzers (Instrumentation Laboratory Company, Bedford, Mass.).In an embodiment, the disclosed flow cell closes to provide chamberhaving an optical path through the chamber having a path-length of about80 micrometers to about 90 micrometers for optical determination of oneor more analytes of a body fluid sample in the chamber. When the flowcell is in the closed configuration for sample analysis, the opticalpath-length through an upper portion of the flow cell and a lowerportion of the flow cell is very accurate due to a very small toleranceof displacement between an upper portion of the flow cell and a lowerportion of the flow cell. When a measurement is complete, the flow cellcan be opened for washing out the body fluid sample from the samplechamber. When the flow cell is in the open configuration for cleaning,the tolerance of displacement between the upper portion of the flow celland the lower portion of the flow cell is not critical and the gapbetween the upper portion and lower portion of the flow cell may besignificantly greater than 80-90 micrometers. In an illustrativeembodiment, when the flow cell is in the open configuration for washout, gap between the upper portion of the flow cell and the lowerportion of the flow cell may provide a chamber depth of about 250-400micrometers, for example.

Aspects of the present disclosure include a floating seal surroundingthe sample chamber. The seal is effective by lateral compression of theseal against sidewalls of a seal channel surrounding the sample chamber.Some extra space is provided above and below the seal in the sealchannel. The extra space prevents the seal from being compressedvertically, or from bottoming-out to form face seal between the topportion and bottom portion of the sample cell.

Sample cell configurations that employ face seals do not exhibitrepeatable measurement lengths within one micron tolerance. By avoidingcompression of the seal between the top portion and bottom portion ofthe sample cell, the disclosed floating seal configuration allows thesample cell to be closed to a repeatable chamber height within about onemicron. This closed chamber height provides an optical measurementdistance that is accurate and repeatable within about one micron in aheight range of about 0.09 mm in some embodiments to about 0.5 mmdistance in other embodiments.

In an illustrative embodiment, closing of the disclosed flow cell may beactuated using low cost shape memory alloy such as nitinol, for example.Alternatively, the flow cell maybe closed by an actuation mechanism thatincludes a solenoid or an electric motor such as a stepper motor, forexample. The flow cell halves are urged away from each other toward theopen configuration by a spring force when the actuation mechanism isretracted or relaxed.

Referring to FIGS. 1A-1C, aspects of the present disclosure include asample cell apparatus 100 for use in spectroscopic determination of ananalyte in a body fluid sample. The sample cell apparatus 100 includes afirst plate member 10 made from an optically clear material and a secondplate member 20 made from an optically clear material and opposing thefirst plate member 10. A first surface of the first plate member 10faces the second plate member 20. The first surface includes a firstwell portion 19, a first seal channel portion 12 adjacent to the firstwell portion 19, and a first abutment surface 15 outside of the firstwell portion 19 and outside of the first seal channel portion 12. Asecond surface of the second plate member 20 faces the first platemember 10. The second surface includes a second well portion 29 alignedwith the first well portion 19 to form a sample chamber 50, a secondseal channel portion 22 aligned with the first seal channel portion 12and adjacent to the second well portion 29, and a second abutmentsurface 25 outside of the second well portion 29 and outside of thesecond seal channel portion 23 and aligned with the first abutmentsurface 15. The first well portion 19 has a fixed depth relative to thefirst abutment surface 15, and the second well portion 29 has a fixeddepth relative to the second abutment surface 25. One or more springmembers 40 are configured between the first plate member 10 and thesecond plate member 20 to urge the first plate member 10 away from thesecond plate member 20. A floating seal 30 extends into the first sealchannel portion 12 and the second seal channel portion 22. The floatingseal 30 is compressed transversely between sidewalls of the first sealchannel and the second seal channel. According to an aspect of thepresent disclosure, the floating seal 30 defines a periphery of thesample chamber. A fluid inlet path 60 extends through the first platemember 10 or the second plate member 20 into the sample chamber 50. Afluid outlet path 70 also extends through the first plate member 10 orthe second plate 20 into the sample chamber 50.

According to another aspect of the present disclosure, the sample cellapparatus 100 includes an actuator member 80 configured to controllablyovercome the spring member(s) to urge the first plate member 10 againstthe second plate member 20 by a displacement defined by abutment betweenthe first abutment surface 15 and the second abutment surface 25.

According to an aspect of the present disclosure, the actuator member 80may include a shape memory member. The shape memory member may be madefrom nitinol, or another shape memory material, for example. Accordingto another aspect of the present disclosure, the actuator member 80 mayinclude an electric motor or a solenoid, for example.

According to another aspect of the present disclosure, the springmembers 40 may be cantilever springs. The cantilever springs may bemonolithically formed with the first plate member 10 and/or the secondplate member 20, for example. According to another aspect of the presentdisclosure, the spring members may be compression springs, or the like.

In certain embodiments, the sample chamber 50 may be elongated. Theinlet path 60 may be located proximate to a first end of the elongatedsample chamber 50, and the outlet path 70 may be located proximate to asecond end of the sample chamber 50 opposite the first end of the samplechamber 50. In certain embodiments, the sample chamber 50 and thefloating seal 30 may be substantially diamond shaped.

According to an aspect of the present disclosure, a light source isdirected through the first plate member 10 into the sample chamber 50. Alight detector apparatus is directed to receive light from the lightsource that has passed through the first plate member 10, the samplechamber 50 and the second plate member 60.

In certain embodiments, the light detector apparatus may be aspectroscope, for example. The light source and/or the light detectormay be integrated with actuator member.

According to an aspect of the present disclosure, the sample cellapparatus 100 may include an outer surface having a detent structureconfigured for engaging a mating detent structure in the actuator member80 for locating the sample cell apparatus relative to the actuatormember and/or relative to the light source and light detector apparatus.

Referring to FIG. 2, in an illustrative embodiment of the disclosed flowcell 200, one or more finger portions 240, 242 are integrally moldedwith the first plate member 210 and the second plate member 220respectively to form cantilever spring members configured to urge thefirst plate member 210 away from the second plate member 210. Thecantilever spring members may be used instead of or in addition tocompression springs (40 in FIGS. 1A-1C), for example. Because the gapdimension between the first plate member and the second plate member isnot as critical while the flow cell 200 is in the open cleaningconfiguration as it is in when the flow cell 200 is in the closedmeasurement configuration, simple spring members such as the describedcantilever spring arms are sufficient to meet design requirements forapplying a separating force. Alternative embodiments may provide aspring force to separate the first plate member from the second platemember with compression springs or an elastomeric pad such as a foamrubber pad, or a combination of spring types, for example.

Referring to FIG. 3, an embodiment of the disclosed flow cell 302 may beconfigured for removably mounting in a test head apparatus 300. The testhead apparatus 300 may include a flow cell support structure 304 and anactuating member 306. The actuating member 306 is configured tocontrollably apply a force to the flow cell 302, which compresses thetop portion 310 of the flow cell 302 against the bottom portion 320 ofthe flow cell by overcoming the separating force of the compressionspring(s) 340. The actuating member 306 may be coupled to one or moremechanical actuators. Various types of mechanical actuators including,pneumatic actuators, hydraulic actuators, electric motors, are wellknown and may suitable for controllably driving the actuating member 360in the test head apparatus, for example.

In an illustrative embodiment, the test head apparatus 300 may alsoinclude a light source configured for directing light though the testcell 302 and a spectrometer configured for receiving light from thelight source that has passed through the test cell 302. The light sourcemay include a neon light source and/or an LED light source for example.The spectrometer may include spectrometer optics and/or a diffuser, forexample.

In another aspect of the disclosure, an optical diffuser may beintegrally part of first plate member 10 and/or the second plate member20 shown in FIGS. 1A-1C, for example. For example, a thin diffuser canbe affixed to the plates or, alternatively, the surface of the platescan be frosted to diffuse the light.

Referring to FIG. 4, according to an aspect of the present disclosure,the disclosed flow cell 406 may include an alignment portion 404 foraligning the flow cell properly when it is mounted in the test headapparatus 400. The alignment portion 404 may include a depression ordetent in the surface of the top portion 410 or bottom portion 420 ofthe flow cell 406. The alignment portion 404 is configured for engagingan alignment and retention portion 402 of the test head apparatus 400.In an illustrative embodiment, the alignment and retention portion 402may include a wheel configured to sit in the depression/detent of thealignment portion 404 of the flow cell 406 when the flow cell 406 isproperly located in the test had apparatus 400. The wheel may be springbiased against the alignment and retention portion 402 of the flow cell406, for example.

Referring to FIG. 5, an embodiment of the disclosed test head apparatus500 includes an actuating member 506 operatively coupled to a nitinolwire 508. The nitinol wire changes length upon application of electricalenergy applied to the nitinol wire, and returns to an original lengthupon removal of the electrical energy. This shape memory characteristicof the nitinol wire enables a simple and reliable electro-mechanicalactuation mechanism for controlling movement of the actuating member 506by applying and removing a voltage and/or electrical current to thenitinol wire.

FIG. 6 is a graph 600 of test data including measurements of the opticalpath length through a flow cell 502 using an embodiment of the test headapparatus as shown in FIG. 5 in which actuation was implemented byenergizing the nitinol wire 508. In this configuration the gap wasrepeatable with +/−1.5 microns.

In previously known optical test heads, a light detector portion of aspectrometer device has typically been mounted in the test head andconnect to an external portion of the spectrometer with a fiber opticcable. This adds cost and complexity to the test head apparatus. Aspectsof the present disclosure include an optical light engine integrated ina test head apparatus. The disclosed integrated optical light enginecombines a light emitting diode (LED), a neon lamp source, aspectrometer, optics with diffuser, and a mechanism for actuating avariable path length flow cell. The disclosed test head apparatus headis compact and rugged and avoids optical fibers for coupling the LED andspectrometer to the test head. The integrated optical head enablesportable blood gas instruments to be constructed with lower costs andgreater simplification, for example.

In one example, disclosure, a small spectrometer, such as modularspectrometer by Ocean Optics, Inc. of Dunedin, Fla., USA, may be mountedin the test head and directly coupled to external processing equipment,for example without employing fiber optic cables. An illustrativeembodiment of the disclosed test head apparatus 700 as shown in FIG. 7,includes a spectrometer 710, such as spectrometer model STS by OceanOptics, Inc., mounted directly in the test head apparatus 700. Thespectrometer 710 is configured for analyzing light that is transmittedthrough a flow cell 702 mounted in the test head apparatus 700. Thedisclosed configuration including an incorporated spectrometer 710 inthe test head apparatus 700 is significantly less expensive thanpreviously known test head configurations that couple a spectrometerlight detector portion to a spectrometer device with expensive fiberoptic cable bundles, for example.

Referring to FIG. 8, another aspect of the present disclosure includes amethod 800 for spectroscopic determination of an analyte in a body fluidsample. At block 810, the method 800 includes providing a sample cellhaving a sample path extending between a first plate member and anopposing second plate member. The sample path is adapted forcommunicating the body fluid sample from a fluid inlet path through asample chamber between the first plate member and the second platemember to a fluid outlet path. At block 820, the method includesinserting the body fluid sample into the chamber. At block 830, themethod 800 includes providing one or more spring members between thefirst plate member and the second plate member. The spring members applya spring force configured to separate the first plate member from thesecond plate member. At block 840, the method 800 includes moving thefirst plate member along a normal axis of the first plate and the secondplate to a closed configuration by applying a compressive force thatovercomes the spring force and urges an abutment surface of the firstplate member against an abutment surface of the second plate member. Inthe closed configuration a predetermined optical path length is providedthrough the sample chamber for conducting optical measurements.

In block 830, the method 800 may also include mechanically limiting thepredetermined optical path length within a range of +/−1 micron based ona first fixed depth of the chamber into the first plate member relativeto the abutment surface of the first plate member and second fixed depthof the chamber into the second plate member relative to the abutmentsurface of the second plate member. According to aspects of the presentdisclosure, the method 800 also includes spectroscopically determiningthe presence of analyte in the sample at block 850 by applying lightalong the predetermined optical path length.

According to aspects of the present disclosure, the method 800 alsoincludes removing the compressive force after spectroscopicallydetermining the presence of the analyte in the body fluid sample at bloc860 and allowing the first plate member to be displaced by the springforce along the normal axis away from the second plate member to an openconfiguration. The method 800 further includes clearing the body fluidsample from the chamber at block 870 while the first plate member isdisplaced away from the second plate member in the open configuration.

What is claimed is:
 1. A sample cell apparatus for use in spectroscopicdetermination of an analyte in a body fluid sample, the sample cellapparatus comprising: a first plate member made from an optically clearmaterial; a second plate member made from an optically clear materialand opposing the first plate member; a first surface of the first platemember facing the second plate member, the first surface comprising afirst well portion, a first seal channel portion adjacent to the firstwell portion, and a first abutment surface outside of the first wellportion and outside of the first seal channel portion; and a secondsurface of the second plate member facing the first plate member, thesecond surface comprising a second well portion aligned with the firstwell portion to form a sample chamber, a second seal channel portionaligned with the second seal channel portion and adjacent to the secondwell portion, and a second abutment surface outside of the second wellportion and outside of the second seal channel portion and aligned withthe first abutment surface, the second abutment surface configured toabut the first abutment surface; wherein the first well portion has afixed depth relative to the first abutment surface and wherein thesecond well portion has a fixed depth relative to the second abutmentsurface; one or more spring members configured between the first platemember and the second plate member and configured to urge the firstplate member away from the second plate member; a floating sealextending into the first seal channel portion and the second sealchannel portion, the floating seal compressed transversely betweensidewalls of the first seal channel and the second seal channel, thefloating seal defining a periphery of the sample chamber; a fluid inletpath extending through the first plate member or the second plate memberinto the sample chamber; and a fluid outlet path extending through thefirst plate member or the second plate member into the sample chamber.2. The sample cell apparatus of claim 1, comprising: an actuator memberconfigured to controllably overcome the at least one spring member andto urge the first plate member against the second plate member by adisplacement defined by abutment between the first abutment surface andthe second abutment surface.
 3. The sample cell apparatus of claim 2,wherein the actuator member comprises a shape memory member.
 4. Thesample cell apparatus of claim 3, wherein the shape memory member ismade from nitinol.
 5. The sample cell apparatus of claim 2, wherein theactuator comprises an electric motor.
 6. The sample cell apparatus ofclaim 2, wherein the actuator comprises a solenoid.
 7. The sample cellapparatus of claim 1, wherein the at least one spring member comprisesat least one cantilever spring.
 8. The sample cell apparatus of claim 7,wherein the at least one cantilever spring is monolithically formed withthe first plate member and/or the second plate member.
 9. The samplecell apparatus of claim 1, wherein the at least one spring membercomprises at least one compression spring.
 10. The sample cell apparatusof claim 1, wherein the sample chamber is elongated.
 11. The sample cellapparatus of claim 10, wherein the inlet path is located proximate to afirst end of the elongated sample chamber, and wherein the outlet pathis located proximate to a second end of the sample chamber opposite thefirst end of the sample chamber.
 12. The sample cell apparatus of claim10, wherein the sample chamber and the floating seal are substantiallydiamond shaped.
 13. The sample cell apparatus of claim 1, comprising: alight source directed through the first plate member into the samplechamber; and a light detector apparatus directed to receive light fromthe light source that has passed through the first plate member, thesample chamber and the second plate member.
 14. The sample cellapparatus of claim 13, wherein the light detector apparatus comprises aspectroscope.
 15. The sample cell apparatus of claim 13, wherein thelight source is integrated with actuator member.
 16. The sample cellapparatus of claim 13, wherein the light detector apparatus isintegrated with the actuator member.
 17. The sample cell apparatus ofclaim 1, comprising an outer surface having a detent structureconfigured for engaging a mating detent structure in the actuator memberfor locating the sample cell apparatus relative to the actuator memberand/or relative to the light source and light detector apparatus, evenwhen the actuator arm is retracted/relaxed.
 18. The sample cellapparatus of claim 1, comprising an optical diffuser integrated on thefirst plate member and/or the second plate member.